Purinergic (P2X) receptors are ATP-gated cation-selective channels. Each receptor is made up of three protein subunits or monomers. To date seven separate genes encoding P2X monomers have been identified: P2X1 (SEQ ID NO: 9), P2X2 (SEQ ID NO: 10), P2X3 (SEQ ID NO: 11), P2X4 (SEQ ID NO: 12), P2X5 (SEQ ID NO: 13), P2X6 (SEQ ID NO: 14), (shown in FIGS. 2 to 7 respectively, herein), and P2X7 (SEQ ID NO: 8; FIG. 1).
P2X7 receptors are of particular interest as the expression of these receptors is understood to be limited to cells having potential to undergo programmed cell death, such as thymocytes, dendritic cells, lymphocytes, macrophages and monocytes. Further, a P2X7 receptor containing one or more monomers having a cis isomerisation at Pro210 of SEQ ID NO: 8 (see FIG. 1), and which is devoid of ATP binding function is found on cells that are understood to be unable to undergo programmed cell death, such as preneoplastic cells and neoplastic cells in the form of many carcinomas and blood cancers.
At least 8 splice variants of P2X7 monomers are known to exist (SEQ ID NOs: 15-22, as depicted in FIGS. 8 to 15, respectively). These include variants having cytoplasmic N and C termini, 2 transmembrane spanning domains and an extra-cellular domain, and variants that have a cytoplasmic N terminus, transmembrane domain and a truncated extra-cellular domain of various lengths.
To date, P2X7 receptors have only been detected in the cytoplasm, the nucleus and anchored to the lipid bilayer of the cell surface membrane by one or more transmembrane spanning domains as discussed above.